A broad group of compounds including substituted pyrazoles, pyrroles, indoles, and carbazoles were screened to identify potential inhibitor lead compounds of fructose-1,6-bisphosphatase (FBPase). Best inhibitors are (1H-indol-1-yl)(4-(trifluoromethyl)phenyl)methanone, ethyl 3-(3,5-dimethyl-1H-pyrrol-2-yl)-4,4,4-trifluoro-3-hydroxybutanoate, 3,5-diphenyl-1-(3-(trifluoromethyl) phenyl)-1H-pyrazole, and ethyl 3,3,3-trifluoro-2-hydroxy-2-(1-methyl-1H-indol-3-yl)propanoate. The IC50 values (3.1, 4.8, 6.1, and 11.9 microM) were comparable to that of AMP, the natural inhibitor of murine FBPase (IC50 of 4.0 microM). Docking programs were utilized to interpret the experiments.